EP0276342A1 - Methode zur Behandlung von Plasma und dessen Produkten - Google Patents

Methode zur Behandlung von Plasma und dessen Produkten Download PDF

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Publication number
EP0276342A1
EP0276342A1 EP87101072A EP87101072A EP0276342A1 EP 0276342 A1 EP0276342 A1 EP 0276342A1 EP 87101072 A EP87101072 A EP 87101072A EP 87101072 A EP87101072 A EP 87101072A EP 0276342 A1 EP0276342 A1 EP 0276342A1
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EP
European Patent Office
Prior art keywords
plasma
blood
immunoadsorbent
antibodies
zone
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP87101072A
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English (en)
French (fr)
Other versions
EP0276342B1 (de
Inventor
Harold C. Mielke
Patrick J. Scannon
Paul R. Sohmer
John C. Klock
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Xoma Corp
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Xoma Corp
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Publication of EP0276342B1 publication Critical patent/EP0276342B1/de
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Expired - Lifetime legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3679—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by absorption
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/16—Blood plasma; Blood serum

Definitions

  • the present invention is a method for treat­ing human blood plasma prior to administering to a pa­tient and, more particularly, is a method for removing blood group antibodies from the plasma to avoid incom direability between donors and recipients of different blood groups.
  • Plasma aqueous solution
  • erythrocytes red cells
  • white cells leukocytes
  • platelets thrombocytes
  • Plasma is the solution which remains after the cells have been removed from the blood.
  • var­ious proteins including antibodies secreted by the white cells as in immunological response to the presence of antigeus in the blood, as well as proteins responsi­ble for other essential physiological processes, such as the clotting factors required for hemostasis.
  • the major human blood group or type is deter­mined by the presence of ABH antigens on the cell sur severelyface of the red blood cells.
  • the antigens are oligosac­charides attached to glycolipids or glycoproteins in the plasma membranes of the red blood cells.
  • the anti­genic structure is of three types, referred to as "A”, "B” and neither "A” nor “B” (that is, “H” or formerly "O”).
  • Either the A antigen, the B antigen, or both the A and B antigen may be present on the surface of an individual's red blood cells. Every individual's blood will contain naturally occurring antibody (primarily IgM) against the ABH antigens which are not present on his red blood cells. The situation is summarized in Table 1, which follows.
  • the present invention provides a method for treating human plasma obtained from any donor which renders the plasma or product compatible with any recip­ient, regardless of the recipient's blood group.
  • the method comprises passing plasma from the donor through an immunoadsorbent zone capable of binding one or more of the antibodies to remove such antibodies.
  • the immu­noadsorbent zone includes receptors specific for both the anti-A and anti-B antibodies, typically anti-(anti-­A) and anti-(anti-B) antibodies or the A and B antigens themselves, immobilized therein.
  • the method requires that the ABH antibodies be substantially completely removed from the product to at least below a level de­tectable by the standard antiglobulin (Coombs) test at a 1:2 dilution, preferably at a 0 dilution.
  • the present invention provides a source of human plasma derived from donors having all blood groups, which may be transfused to recipients regardless of blood group.
  • the method may be practiced in a hospital or blood bank to avoid having to segregate plasma by blood group for storage so that a particular plasma is not administered to a recipient having an incompatble blood type.
  • the method will also find use under emer­gency situations where a limited number of blood donors are available and where, in the absence of such a treat­ment method, plasma might be unavailable for certain individuals needing transfusions.
  • the method of the present invention employs an immunoadsorbent zone having receptor specific for at least anti-A or anti-B antibodies, prefereably having receptors for both such antibodies, immobilized therein.
  • an immunoadsorbent zone having receptor specific for at least anti-A or anti-B antibodies, prefereably having receptors for both such antibodies, immobilized therein.
  • the receptors may be naturally occurring or synthetic compounds which have the capability of speci­fically binding the anti-A and anti-B antibodies and which may be immobilized within a permeable medium to form the immunoadsorbent zone.
  • Particularly useful are naturally occurring A and B cell surface antigens, and antibodies raised against both the anti-A and anti-B antibodies, that is, anti-(anti-A) and anti-(anti-B) antibodies.
  • Such antibodies may be obtained in a con­ventional manner by hyperimmunizing any one of various mammals, such as rabbits, sheep, mice, goats, and the like, and purifying the antisera obtained.
  • monoclonal antibodies may be produced by the method described by Kohler and Milstein, (1976) Nature 356:495-497. Such techniques for preparing antibodies are well known in the art and do not form part of the present invention.
  • the preferred receptors for the present inven­tion are artificially synthesized human blood group A and B antigens prepared in the manner described by Lemieux, "Human Blood Groups and Carbohydrate Chemis­try,” (1978) Chem. Soc. Rev., pp 423-452.
  • the immunoadsorbent zone of the present inven­tion comprises the receptor immobilized on a solid phase immunoadsorbent material.
  • a solid phase immunoadsorbent material may be selected from a wide variety of materials, typi­cally silicates or water insoluble polymers used to load a separation column, or water permeable membranes.
  • the immobile solid phase of the present invention must be capable of covalently or non-covalent­ly binding the specific receptors for the anti-A and anti-B antigens and must be biocompatible with human blood.
  • Suitable materials include silica gels, glass beads, cross-linked dextrans, polyacrylamides and other biologically inert materials which can be derivatized, typically aminated, for immobilizing the receptors of interest.
  • the receptors may be immobilized in the immu­noadsorbent zone by a variety of conventional techniques, depending in particular on the nature of the binding material. In general, it is necessary to modify one or more functionalities on the immunoadsorbent material to allow coupling to the receptor.
  • the covalent binding of proteins to immunoadsorbent materials, in particular antibodies, is taught in U.S. Patents Nos. 3,555,143 and 4,108,974.
  • artificial antigen includes a glycosidic union to the 8-methoxycar­bonyloctyl alcohol which can serve as a bridging arm for attachment to the solid support.
  • the antigen is reacted with acyl hydrazide to form the acyl azide which is then allowed to react with an aminated solid support or with a suitable amine on any solid material.
  • the plasma is obtained by separating the red cells, white cells and platelets from the whole blood by well-known techniques. Once the plasma is obtained, it may be treated directly or may be stored and treated at a later time.
  • the immunoadsorbent column or membrane Prior to passing plasma therethrough, the immunoadsorbent column or membrane is preferably treated to inhibit non-specific protein adsorption. This may be accomplished by washing the immunoadsorbent zone with a colloidal xylan solution (collodion) or with a saline solution containing 1% human serum albumin, and incubating the zone, preferably overnight, with the wash solution at 4°C. The column is then washed with saline solution prior to treatment of the plasma.
  • a colloidal xylan solution colloidal xylan solution
  • a saline solution containing 1% human serum albumin a containing 1% human serum albumin
  • the plasma is passed through the immunoad­sorbent zone at a rate chosen so that the final concen­tration of anti-A and anti-B antibodies is undetectable by the standard antiglobulin (Coombs) test at a maximum dilution of 1:2, preferably at a zero dilution.
  • the standard antiglobulin (Coombs) test is described in Mollison, (1972) "Blood Transfusion in Clinical Medi­cine,” Blackwell Scientific Publications, Oxford pp. 420-428.
  • the plasma or plasma fraction can be stored or used in the conventional man­ner.
  • the blood products particularly antihemophilic factor, activated prothrombin complex and the like, it will often be desirable to further treat the product, such as by lyophilization, to inhibit degradation.
  • Carbohydrate antigen (B-trisaccharide) pre­pared as described by Lemieux, supra , was bound to crys­talline silica (synsorb A) and unhaptenated silica (Chembiomed, Ltd., Edmonton, Canada) according to the manufacturer's recommendations.
  • One gram of the silica with 10 micromoles of bound antigen were placed in a cartridge suitable for passing plasma.
  • Plasma was obtained from ten normal, healthy donors, free from all medication for at least 14 days. Plasma (10 ml) from each donor was applied to a fresh cartridge over a five minute period, and the treated samples collected for analysis.
  • Coagulation parameters were also measured, as set forth in Table 2. The values given are the average for all ten donors.
  • Prothrombin time is the time re­quired to convert prothrombin to thrombin. No signifi­cant deterioration was observed in this parameter.
  • PTT is partial thrombo-plastin time. Although there was some increase in this parameter which may be attribut­able to partial adsorption of one or more clotting factors, the increase is not clinically significant. Similarly, the decreases in Factor VIII (antihemophilic factor), Factor V (proaccelerin), and fibrinogen, are likely due to non-specific adsorption, but are well within the limits for useful plasma.
  • Table 3 sets forth the concentrations of immu­noglobulins and ratio of albumins to globulins in the plasma before and after treatment.
  • the drop in IgM levels (and to a lesser extent IgG levels) is to be expected since the anti-(ABH antigen) antibodies are primarily IgM.
  • the reduction in immunoglobulins would also account for the increase in the albumin/globulin ratio.
  • Table 4 sets forth the results of quantitative electrophoretic measurement of five specific proteins, as well as total protein, in both pre-treatment and post-treatment plasma. The average value for all ten donors is given. The only significant change is found in the decrease of immunoglobulins, as would be expected since the process is directed at immunoglobulin removal.
  • Table 5 shows the effect of both pre-treatment and post-treatment plasma on platelet aggregation and serotonin release, in the presence of known activating factors (adenosine diphosphate (ADF), epinephrine, T50 max, and collagen). The effect of the treatment on these essential clotting functions is not significant.
  • ADF adenosine diphosphate
  • epinephrine epinephrine
  • T50 max epinephrine
  • a method for treating blood plasma to substantially completely remove anti-­(ABH antigen) antibodies from plasma prior to transfu­sion Such treated plasma can be administered to recip­ients without regard to blood type.
  • the treated plasma retains substantially all other blood proteins measured from the standpoint of clinical sig­nificance, ensuring that the plasma will be fully capa­ble of physiological activity in the recipient.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Hematology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Cell Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Cardiology (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Virology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Anesthesiology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
EP87101072A 1984-07-19 1987-01-27 Methode zur Behandlung von Plasma und dessen Produkten Expired - Lifetime EP0276342B1 (de)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US06/632,756 US4664913A (en) 1982-05-24 1984-07-19 Method for treating plasma for transfusion

Publications (2)

Publication Number Publication Date
EP0276342A1 true EP0276342A1 (de) 1988-08-03
EP0276342B1 EP0276342B1 (de) 1992-04-01

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EP87101072A Expired - Lifetime EP0276342B1 (de) 1984-07-19 1987-01-27 Methode zur Behandlung von Plasma und dessen Produkten

Country Status (7)

Country Link
US (1) US4664913A (de)
EP (1) EP0276342B1 (de)
AT (1) ATE74282T1 (de)
AU (1) AU596392B2 (de)
DE (1) DE3778002D1 (de)
ES (1) ES2032276T3 (de)
GR (1) GR3004763T3 (de)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0572194A1 (de) * 1992-05-28 1993-12-01 The New York Blood Center, Inc. Entfernung von Antikörpern aus von Blut stammenden Zusammensetzungen unter Erhalt von Gerinnungsfaktoren
US8865172B2 (en) 2000-05-08 2014-10-21 Advanced Extravascular Systems, Inc. Method for reducing the number of unwanted molecules in bodily fluids
EP2345425B1 (de) 2005-12-26 2018-07-11 Laboratoire Français du Fractionnement et des Biotechnologies Immunglobulin g (igg)-konzentrat mit depletion von anti-a- und anti-b-antikörpern und polyreaktiven igg
WO2022073966A3 (de) * 2020-10-06 2022-07-21 Universität Greifswald Verfahren und vorrichtung zur herstellung von universalplasma

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5061237A (en) * 1985-07-02 1991-10-29 Cytomed Medizintechnik Gmbh Method of purifying whole blood
JPH0662436B2 (ja) * 1986-05-19 1994-08-17 株式会社ミドリ十字 静注用免疫グロブリン製剤の製造方法
US5122112A (en) * 1986-11-21 1992-06-16 Imre Corporation Antigen-specific removal of circulating immune complexes
US5147289A (en) * 1990-03-29 1992-09-15 Therakos, Inc Non-specific immune system enhancement
EP0896824A1 (de) * 1997-08-05 1999-02-17 Octapharma Ag Universell verwendbares Bluttplasma
US20020182195A1 (en) * 1997-08-05 2002-12-05 Octapharma Ag Universally applicable blood plasma
US6620382B1 (en) 1998-05-22 2003-09-16 Biopheresis Technologies, Llc. Method and compositions for treatment of cancers
US8197430B1 (en) 1998-05-22 2012-06-12 Biopheresis Technologies, Inc. Method and system to remove cytokine inhibitor in patients
CA2385179A1 (en) * 1999-10-08 2001-04-19 David J. Hammond Isoagglutinin-depleted blood compositions and methods of making same
US6379708B1 (en) * 1999-11-20 2002-04-30 Cytologic, Llc Method for enhancing immune responses in mammals
CN1207004C (zh) * 2001-04-18 2005-06-22 马建川 通用型冻干血浆及其制备方法
EP1420641A4 (de) * 2001-08-01 2005-05-25 Anil K Chauhan Immunkomplexe
WO2004071446A2 (en) * 2003-02-12 2004-08-26 Chauhan Anil K Immune complexes
ES2281848T3 (es) * 2003-12-19 2007-10-01 Octapharma Ag Plasma sanguineo universalmente aplicable, virus inactivado producido a partir de porciones de plasma de no caucasicos.
DK1949915T3 (da) * 2004-04-30 2012-11-26 Biopheresis Technologies Inc Fremgangsmåde og system til fjernelse af opløselig TNFR1, TNRF2 og IL2R i patienter
US20070065514A1 (en) * 2005-09-22 2007-03-22 Howell Mark D Method for enhancing immune responses in mammals
US20080075690A1 (en) * 2006-09-22 2008-03-27 Mark Douglas Howell Method for enhancing immune responses in mammals
US8449520B2 (en) * 2007-03-19 2013-05-28 HemCon Medical Technologies Inc. Apparatus and methods for making, storing, and administering freeze-dried materials such as freeze-dried plasma
US7776022B2 (en) * 2007-03-19 2010-08-17 Hemcon Medical Technologies Apparatus and methods for making, storing, and administering freeze-dried materials such as freeze-dried plasma
US20090107001A1 (en) * 2007-03-19 2009-04-30 Hemcon Medical Technologies, Inc. Apparatus and methods for making, storing, and administering freeze-dried materials such as freeze-dried plasma
US20090223080A1 (en) * 2007-03-19 2009-09-10 Hemcon Medical Technologies, Inc. Apparatus and methods for making, storing, and administering freeze-dried materials such as freeze-dried plasma
FR3035799B1 (fr) 2015-05-06 2017-05-05 Elicityl Support pour la purification de liquides biologiques
FR3035794B1 (fr) 2015-05-06 2017-05-05 Elicityl Procede pour la purification du sang total ou d'un produit issu du sang
US10697983B2 (en) 2015-09-08 2020-06-30 Merck Patent Gmbh Methods of evaluating quality of media suitable for removing anti-A or anti-B antibodies
US10697982B2 (en) 2015-09-08 2020-06-30 Merck Patent Gmbh Methods of evaluating quality of a chromatography media which binds anti-A or anti-B antibodies
JP7110360B2 (ja) 2017-10-09 2022-08-01 テルモ ビーシーティー バイオテクノロジーズ，エルエルシー 凍結乾燥方法
JP7471316B2 (ja) 2019-03-14 2024-04-19 テルモ ビーシーティー バイオテクノロジーズ，エルエルシー マルチパート凍結乾燥容器

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0108658A1 (de) * 1982-09-24 1984-05-16 Institut National De La Sante Et De La Recherche Medicale (Inserm) Vorrichtung zur Entfernung oder zur Gewinnung von Antikörpern oder Antigenen aus Blut, ihre Herstellung und Verwendung

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AT399095B (de) * 1986-03-27 1995-03-27 Vukovich Thomas Dr Verfahren zur auftrennung von proteinen mittels gradientenelution und vorrichtung zur durchführung des verfahrens

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0108658A1 (de) * 1982-09-24 1984-05-16 Institut National De La Sante Et De La Recherche Medicale (Inserm) Vorrichtung zur Entfernung oder zur Gewinnung von Antikörpern oder Antigenen aus Blut, ihre Herstellung und Verwendung

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0572194A1 (de) * 1992-05-28 1993-12-01 The New York Blood Center, Inc. Entfernung von Antikörpern aus von Blut stammenden Zusammensetzungen unter Erhalt von Gerinnungsfaktoren
US5541294A (en) * 1992-05-28 1996-07-30 New York Blood Center, Inc. Removal of antibodies from blood-derived compositions while retaining coagulation factors
US8865172B2 (en) 2000-05-08 2014-10-21 Advanced Extravascular Systems, Inc. Method for reducing the number of unwanted molecules in bodily fluids
EP2345425B1 (de) 2005-12-26 2018-07-11 Laboratoire Français du Fractionnement et des Biotechnologies Immunglobulin g (igg)-konzentrat mit depletion von anti-a- und anti-b-antikörpern und polyreaktiven igg
WO2022073966A3 (de) * 2020-10-06 2022-07-21 Universität Greifswald Verfahren und vorrichtung zur herstellung von universalplasma

Also Published As

Publication number Publication date
GR3004763T3 (de) 1993-04-28
AU6804987A (en) 1988-08-04
AU596392B2 (en) 1990-05-03
US4664913A (en) 1987-05-12
ES2032276T3 (es) 1993-02-01
ATE74282T1 (de) 1992-04-15
EP0276342B1 (de) 1992-04-01
US4664913B1 (de) 1990-01-30
DE3778002D1 (de) 1992-05-07

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